Project Summary/Abstract Obesity rates are rapidly rising, as are related health and quality-of-life complications. As such, gaining a better understanding of the mechanisms involved in the development and maintenance of obesity is critical. Because diet and eating behaviors are core contributors to weight gain, an improved understanding of these processes is required. A key variable in these processes that is currently poorly understood is the effect of sex. Sex- based differences in eating behaviors are consistently observed in both animal and human studies. To date, however, these differences, and their impact on our understanding of the mechanisms of eating behavior, have not been well studied. Failure to study sex effects in this context substantially limits our understanding of these important mechanisms, can result in unnecessary replication of research, and may contribute to problems of reproducibility in clinical research. As such, investigating sex-specific biological processes will lead to a better understanding of underlying mechanisms and will be a critical step in understanding how these mechanisms translate to behavior. Sex differences in eating behaviors involve a number of factors, such as gonadal hormones, social pressures, and physical activity engagement. These factors also interact with neuronal processes involved in eating behaviors. A clear understanding of sex differences in neuronal mechanisms underlying food intake behaviors has yet to be established. While previous studies have examined sex differences in neuronal response to food cues, results have been inconsistent. Disparities may be due to insufficient sample sizes, lack of menstrual cycle phase consistency, and lack of controlled food intake behavior. Hedonic eating, or eating beyond homeostatic needs, may be particularly associated with obesity. As such, identifying sex differences in neurobiology underlying hedonic eating is of particular relevance. To this end, we recently completed a preliminary investigation of sex differences in neuronal responses to food cues with high (vs. neutral) hedonic value, in both fasted and fed states. Sex differences were observed in the fasted state, with greater responses in women than men in the nucleus accumbens and insula, brain regions with prominent roles in food-related reward processing. This may indicate that women are more sensitive to rewarding aspects of foods when fasted. The overall goal of this application is to expand on our initial findings to better understand sex-based differences in the neurobiology underlying hedonic eating behaviors and food-based reward processing, how gonadal hormones contribute to these differences, and how this translates to real-life eating behaviors.